Mechanism of Asymmetric Organocatalysis by Planar Chiral Pyridines of the Addition of Nucleophiles to Ketenes

由于金属类似物的购买和处理成本高，小型非金属有机催化剂的发展变得越来越重要。因此，在过去的五年中，包括手性Bronsted酸在内的用于不对称合成的小分子有机催化剂的开发得到了相当大的关注。据推测，Bronsted酸催化剂的不对称催化作用涉及催化剂和底物之间的质子转移，但其机理迄今尚未得到严格的探讨。迄今为止，一个给定的Bronsted催化剂的成功高度依赖于底物和溶剂，很少有广泛成功的催化剂存在。如果没有更好的机理理解，优化现有催化剂和设计新的更好的催化剂仍然有很大的空间。本研究计划将利用溶液动力学和结构-活性方法解决有关Bronsted酸有机催化的几个关键机制问题。物理有机化学/从物理化学中（历史上）采用定量工具来解决机制问题或理解性质的应用，起源于英国并蓬勃发展了几十年。然而，现在人们认识到，在过去的二十年中，POC已经跟不上合成化学的发展。目前的提议代表了一个理想的情况下，详细的POC动力学和结构-活性研究可以在催化剂开发的关键早期阶段进行。

The development of small non-metal organocatalysts is becoming increasingly important given the frequent high cost of purchase and disposal of metal-analogues. As a result the development of small molecule organocatalysts including chiral Bronsted acids for asymmetric synthesis has gained considerable attention over the past five years. Asymmetric catalysis by Bronsted acid catalysts is presumed to involve proton transfer between catalyst and substrate, however the mechanism has not been rigorously probed thus far. To date, the success of a given Bronsted catalyst is highly substrate and solvent dependent and few broadly successful catalysts exist. There remains ample scope for optimisation of existing catalysts and design of new better catalysts, which is unachievable without a better mechanistic understanding. This research proposal will address several key mechanistic questions about Bronsted acid organocatalysis using solution kinetics and structure-activity approaches.Physical-organic chemistry/the application of quantitative tools taken (historically) from physical chemistry to the solution of problems in mechanisms or in understanding properties-originated and flourished in the UK for several decades. However it is now recognized that in the last twenty years POC has fallen out of step with developments in synthetic chemistry. The present proposal represents an ideal case where detailed POC kinetic and structure-activity studies can be conducted at the crucial early stages of catalyst development.